key: cord-0990354-pjle3zsl authors: Bozzi, Giorgio; Lombardi, Andrea; Ludovisi, Serena; Muscatello, Antonio; Manganaro, Lara; Cattaneo, Dario; GORI, Andrea; Bandera, Alessandra title: TRANSIENT INCREASE OF PLASMA HIV RNA AFTER COVID-19 VACCINATION WITH mRNA-1272 date: 2021-10-16 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2021.10.021 sha: ffce5c491ecb7f1714c14a50d0114c576324ff98 doc_id: 990354 cord_uid: pjle3zsl nan 1 Highligts  COVID-19 vaccination is a promising tool to control the SARS-CoV-2 pandemic  Vaccinations in PLWHIV have been associated with transient HIV-RNA increase  We report a case of transient non-suppressible viremia after COVID-19 vaccination Dear Editor, The latent viral reservoir is the main obstacle preventing HIV eradication, as the virus persists integrated in long-lived, quiescent cells. Immune stimulatory by their nature, vaccines have been evaluated as possible agents for "shock and kill" strategies, which rely on using latency reversing agents to activate HIV transcription and virion production in order to purge the reservoir. Due to the SARS-CoV-2 pandemic, unprecedented efforts towards public health interventions have been made globally, and a constantly growing proportion of individuals have received various vaccines against COVID-19, including those developed employing the novel mRNA technology [Polack et al., 2020; Baden et al., 2021] . Despite having shown good efficacy and safety in people living with HIV (PLWH), and being recommended by national and international HIV societies, the effect of such compounds on HIV latency has yet to be evaluated [https://www.eacsociety.org/home/eacs-statement-15-january-2021/]. Here, we report the case of a man living with HIV who, having previously achieved stable viral suppression, experienced a transient period of non-suppressible viremia after receiving a dose of COVID-19 vaccine. The patient, a 65-year-old heterosexual male, was diagnosed with HIV infection in March 2020, during a diagnostic workup for chronic liver disease due to former alcohol abuse. At diagnosis, plasma HIV RNA (viral load, VL) was 5,780,000 copies/mL and CD4+ count was 44/µL (3.6%, CD4/CD8 0.1%). No coinfections were diagnosed. Antiretroviral treatment (ART) with tenofovir alafenamide/emtricitabine/bictegravir was started two weeks after diagnosis, and was well tolerated; adherence was optimal, as assessed through visit interviews. Three months after ART initiation, VL was below 200 copies/mL and CD4+ count was > 200/µL. Six months after initiation (October 2020) the patient achieved VL suppression (< 50 copies/mL), confirmed by three subsequent determinations. In April 2021 the patient, by then suppressed for more than 6 months, with negative clinical history and negative anti-N antibodies for SARS-CoV-2, received the first dose of mRNA-1273 vaccine (Moderna Biotech), which was also well tolerated (as the patient did not report any systemic side effect), in the context of the Italian vaccination campaign. Twenty-eight days later, before receiving the second dose scheduled on the same day, his blood samples were acquired in our outpatient HIV clinic for his quarterly routine bloodwork. HIV VL was 1,790 copies/mL, the patient was asymptomatic and blood chemistry was normal. Counseling was arranged. Questioned, the patient once again reported optimal adherence. Potential drug-drug interactions were screened and ruled out. Adherence to ART was indirectly confirmed by therapeutic drug monitoring, showing tenofovir trough concentrations (21 ng/L) within the expected range for TAF (10-25 ng/mL) on a leftover blood sample obtained on the same day viremia was assessed [Cattaneo et al., 2020] . Fourteen days after the increase (and the second vaccine dose), a new bloodwork was obtained and VL was suppressed again. Previous studies have found transient increases in HIV VL after vaccination for influenza, S. pneumoniae, and HBV among others, whereas others have shown no effect [Brichacek et al., 1996; Cheeseman et al., 1996; Glesby et al., 1996; Tasker et al., 1998; Viganò et al., 1998 ]. When observed, most VL increases occurred 7-14 days after vaccination [Yek et al., 2016] . A recent randomized controlled trial compared the effect of several vaccination schedules versus placebo in suppressed PLWH, not finding effects on plasma RNA, but observing an increase in HIV cell-associated RNA, CD4+ and CD8+ T-cell activation markers, as well as HIV-specific CD8+ responses [Yek et al., 2016] . The most likely mechanism explaining the increased HIV transcription observed in the context of standard vaccines administered to ART-suppressed PLWH is a generalized inflammatory response with cytokine production, able to activate bystander cells harboring latent HIV, rather than activation of infected vaccine-specific T cells [Posthouwer et al., 2004; Yek et al., 2016] . Furthermore, recent work showed CD4+ T cell cross-reactivity between seasonal coronaviruses and SARS-CoV-2 in vaccine recipients [Woldemeskel et al, 2021] . However, the interplay of mRNA vaccines, the immune system and latent HIV infection is yet to be thoroughly understood. Of note, C-reactive protein quantification was negative in our case; however, we might have documented the descending phase of a curve, as VL determination was at 28 days. To the best of our knowledge, this is the first report of plasma HIV RNA increase after a mRNA COVID-19 vaccine in a patient with documented adherence, possibly reflecting induced proviral transcription. Peculiarities of the case were advanced HIV infection with high baseline VL set-point (6.7 log10) before a relatively recently started ART, which may reflect a larger reservoir size, that could have contributed to the observed transient increase in VL upon generalized stimulation. In the context of mass vaccination, our observation might be of use to guide the clinical practice of other physicians observing unexplained VL increases in ARV-adherent PLWH. Further studies are needed to evaluate whether novel mRNA vaccines have the potential to perturb the latent HIV reservoir, which would be beneficial for the design of future eradication strategies. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine Polish Scientific AIDS Society and Portuguese Association for the clinical study of AIDS (APECS) -Statement on risk of COVID-19 for people living with HIV (PLWH) and SARS-CoV-2 vaccine advice for adults living with HIV Increased plasma human immunodeficiency virus type 1 burden following antigenic challenge with pneumococcal vaccine Impact of Therapeutic Drug Monitoring of Antiretroviral Drugs in Routine Clinical Management of People Living With HIV: A Narrative Review Ellison RT 3rd. Hepatitis B vaccination and plasma HIV-1 RNA The effect of influenza vaccination on human immunodeficiency virus type 1 load: a randomized, double-blind, placebo-controlled study Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine Influenza and pneumococcal vaccination as a model to assess C-reactive protein response to mild inflammation Effects of influenza vaccination in HIV-infected adults: a doubleblind, placebo-controlled trial Immunization with both T cell-dependent and T cell-independent vaccines augments HIV viral load secondarily to stimulation of tumor necrosis factor alpha SARS-CoV-2 mRNA vaccines induce broad CD4+ T cell responses that recognize SARS-CoV-2 variants and HCoV-NL63 Standard vaccines increase HIV-1 transcription during antiretroviral therapy Acknowledgments and authors contributions: GB was involved in the patient's care and conceived and drafted the present work. AL and SL were involved in clinical decisions and contributed to the writing of the manuscript. LM and DC performed laboratory work and contributed to the writing of the manuscript. AM, AB and AG took part of multidisciplinary group discussion, and revised the manuscript critically for important intellectual content. All authors revised the existing literature and approved the final version of the manuscript. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.